Critical host factors that protect the RPE from oxidative injury may determine its susceptibility to tissue destruction or modify the intensity of inflammatory reaction associated with AMD. RPE cell apoptosis and basal deposits, or accumulations of heterogeneous debris in Bruch membrane,Perifosine are two critical histopathologic changes that are well recognized to occur during the development of early AMD. We used these established changes as endpoints for a study designed to determine if cigarette smoke induces evidence of changes associated with AMD. Mice were exposed to 6 months of cigarette smoke in a chamber that produces emphysema with evidence of oxidative damage. In this manuscript, we explored whether mice exposed to cigarette smoke developed these two cardinal features of early AMD using this protocol. The RPE of 8 mo old mice raised in air appeared healthy with normal basolateral infoldings. Bruch membrane maintained a pentalaminar structure composed of the RPE basement membrane, inner collagenous layer,PF-04217903 middle elastic layer, outer collagenous layer, and basement membrane. The chorio-capillaris endothelium appeared healthy with fenestrations. We chose RPE basolateral infoldings and cytoplasmic vacuoles as indicators of RPE cell degeneration because loss of basal infoldings is a marker of epithelial injury and cytoplasmic vacuoles have been identified in RPE that overlie drusen deposits. Figure 2 also shows an 8 mo old mouse that has been exposed to chronic cigarette smoke exhibiting ultrastructural injury to the RPE-Bruch membrane. The RPE basolateral infoldings are dilated and fewer in number, and contain large cytoplasmic vacuoles. Bruch membrane shows an outer collagenous layer deposit while the choriocapillaris has focal loss of fenestrations. In this study, we observed injury to the RPE and Bruch membrane of mice after chronic exposure to cigarette smoke. The RPE had specific ultrastructural changes that are associated with injury that have been observed in AMD. RPE apoptosis is an established change in aging, early AMD, and later stages of AMD such as geographic atrophy.